Mechanisms Underlying the Use of Abusive and Neglectful Behaviors in Dementia Caregiving: The Role of Caregiver Mental Health.

Purpose: In dementia family caregiving, caregiver psychopathology has been frequently identified as a possible risk factor for the use of physically abusive, psychologically abusive, and neglectful behaviors toward care recipients. Yet, the mechanistic role of psychopathology in the use of these behaviors is not understood. The purpose of the current study is to determine the role of caregiver mental health in their daily risk of engaging in physically and psychologically aggressive and neglectful behaviors toward their care recipient with dementia.

Patterns of Family Conflict and Accusations of Abuse in Dementia Family Caregivers: A Latent Class Analysis.

Background And Objectives: Family conflict is a stressor for dementia family caregivers, yet its impact may differ based on the relationship between caregivers and their recipients. This study's objectives were to categorize caregivers into groups based on family conflict, examine whether the relationship to the recipient influences group membership, and determine whether these groups are associated with engaging in abusive and neglectful behaviors.

Research Design And Methods: This national, cross-sectional study of 453 dementia family caregivers used latent class analysis to generate groups based on family conflict and abuse accusations.

ATAD1 prevents clogging of TOM and damage caused by un-imported mitochondrial proteins.

Mitochondria require the constant import of nuclear-encoded proteins for proper functioning. Impaired protein import not only depletes mitochondria of essential factors but also leads to toxic accumulation of un-imported proteins outside the organelle. Here, we investigate the consequences of impaired mitochondrial protein import in human cells.

The Eμ-Ret mouse is a novel model of hyperdiploid B-cell acute lymphoblastic leukemia.

The presence of supernumerary chromosomes is the only abnormality shared by all patients diagnosed with high-hyperdiploid B cell acute lymphoblastic leukemia (HD-ALL). Despite being the most frequently diagnosed pediatric leukemia, the lack of clonal molecular lesions and complete absence of appropriate experimental models have impeded the elucidation of HD-ALL leukemogenesis. Here, we report that for 23 leukemia samples isolated from moribund Eμ-Ret mice, all were characterized by non-random chromosomal gains, involving combinations of trisomy 9, 12, 14, 15, and 17.

Targetable lesions and proteomes predict therapy sensitivity through disease evolution in pediatric acute lymphoblastic leukemia.

Childhood acute lymphoblastic leukemia (ALL) genomes show that relapses often arise from subclonal outgrowths. However, the impact of clonal evolution on the actionable proteome and response to targeted therapy is not known. Here, we present a comprehensive retrospective analysis of paired ALL diagnosis and relapsed specimen.

Adaptation of the Th-MYCN Mouse Model of Neuroblastoma for Evaluation of Disseminated Disease.

High-risk neuroblastoma remains a profound clinical challenge that requires eradication of neuroblastoma cells from a variety of organ sites, including bone marrow, liver, and CNS, to achieve a cure. While preclinical modeling is a powerful tool for the development of novel cancer therapies, the lack of widely available models of metastatic neuroblastoma represents a significant barrier to the development of effective treatment strategies. To address this need, we report a novel luciferase-expressing derivative of the widely used Th-MYCN mouse.

Centrosome Amplification Is a Potential Molecular Target in Paediatric Acute Lymphoblastic Leukemia.

Acute lymphoblastic leukemia (ALL) is the most common form of cancer in children, with most cases arising from fetal B cell precursor, termed B-ALL. Here, we use immunofluorescence analysis of B-ALL cells to identify centrosome amplification events that require the centrosome clustering pathway to successfully complete mitosis. Our data reveals that primary human B-ALL cells and immortal B-ALL cell lines from both human and mouse sources show defective bipolar spindle formation, abnormal mitotic progression, and cell death following treatment with centrosome clustering inhibitors (CCI).

Pragmatic Randomized Control Trial of a Coordinated Community Response: Increasing Access to Services for At-Risk Older Adults.

Background: Elder abuse, neglect, and financial exploitation (EANF) impacts over five million community-dwelling older adults. Yet, no evidence-based intervention models exist that prevent EANF.

Objectives: In this article, we describe the assessment of process outcomes for a Community Complex Care Response Team (C3RT) model developed, via a practitioner-researcher partnership, to reduce instances of EANF victimization among higher risk community-dwelling older adults by identifying and coordinating their service needs.

Early Stages of COVID-19 Pandemic Had No Discernable Impact on Risk of Elder Abuse and Neglect Among Dementia Family Caregivers: A Daily Diary Study.

Unlabelled: There is widespread concern that elder abuse and neglect (EAN) incidents increased during the onset of the COVID-19 pandemic due in part to increases in risk factors. Initial reports relying on administrative systems such as adult protective services records produced mixed results regarding whether or not there was a change in EAN incidents. Using data from an ongoing longitudinal study on EAN in dementia family caregiving that started before the pandemic, we assessed the hypothesis that the pandemic is related to a change in probability of EAN and EAN protective factors.

Pathogenic BRCA1 variants disrupt PLK1-regulation of mitotic spindle orientation.

Preneoplastic mammary tissues from human female BRCA1 mutation carriers, or Brca1-mutant mice, display unexplained abnormalities in luminal differentiation. We now study the division characteristics of human mammary cells purified from female BRCA1 mutation carriers or non-carrier donors. We show primary BRCA1 mutant/+ cells exhibit defective BRCA1 localization, high radiosensitivity and an accelerated entry into cell division, but fail to orient their cell division axis.

Modification of BRCA1-associated breast cancer risk by HMMR overexpression.

Breast cancer risk for carriers of BRCA1 pathological variants is modified by genetic factors. Genetic variation in HMMR may contribute to this effect. However, the impact of risk modifiers on cancer biology remains undetermined and the biological basis of increased risk is poorly understood.

Development and Implementation of a Coordinated Community Response to Address Elder Abuse and Neglect.

Background: Elder abuse, neglect, and financial exploitation impacts over five million community-dwelling older adults in the United States. Although services are available to help these victims, they are often fragmented within communities with service providers having limited means to provide preventative services. The coordinated community response (CCR) is a type of coalition intended to overcome siloed services through a single-point-of-entry system and more team-based approaches to prevention.

Dynamic structural equation modelling evaluating the progressively lowered stress threshold as an explanation for behavioural symptoms of dementia.

Aim: To evaluate the progressively lowered stress threshold (PLST) conceptual model as an explanation for behavioural symptoms of dementia and test several of its hypothesized propositions. The PLST model suggests that due to impairments in coping, persons living with dementia have a reduced threshold for stress and respond with more behavioural symptoms of dementia as stress accumulates throughout the day.

Design: Intensive longitudinal design.

Criminal Protection Orders Among Women Victims of Intimate Partner Violence: Women's Experiences of Court Decisions, Processes, and Their Willingness to Engage With the System in the Future.

Consistent with a therapeutic jurisprudence framework, court decisions and processes can have a therapeutic or antitherapeutic effect on intimate partner violence (IPV) victims. To maximize therapeutic effects, IPV scholars have advocated for survivor-defined practices that emphasize the importance of engaging with victims in a collaborative manner that promotes autonomy, choice, and control. However, limited research exists in the context of criminal protection orders (POs).

A cross-standardized flow cytometry platform to assess phenotypic stability in precursor B-cell acute lymphoblastic leukemia (B-ALL) xenografts.

With the continued poor outcome of relapsed acute lymphoblastic leukemia (ALL), new patient-specific approaches for disease progression monitoring and therapeutic intervention are urgently needed. Patient-derived xenografts (PDX) of primary ALL in immune-deficient mice have become a powerful tool for studying leukemia biology and therapy response. In PDX mice, the immunophenotype of the patient's leukemia is commonly believed to be stably propagated.

General Offending and Intimate Partner Violence Perpetration in Young Adulthood: A Dutch Longitudinal Study.

This study examines the relationship between general offending and intimate partner violence (IPV) perpetration in young adulthood, using a Dutch longitudinal study. Young adults were followed over four waves, and self-reported data on general offending, IPV perpetration, and a number of individual characteristics were collected. Results of random effects models demonstrated that young adults involved in more diverse offending behavior reported higher levels of different types of IPV perpetration, even when individual factors were taken into account.

PDX models reflect the proteome landscape of pediatric acute lymphoblastic leukemia but divert in select pathways.

Background: Murine xenografts of pediatric leukemia accurately recapitulate genomic aberrations. How this translates to the functional capacity of cells remains unclear. Here, we studied global protein abundance, phosphorylation, and protein maturation by proteolytic processing in 11 pediatric B- and T- cell ALL patients and 19 corresponding xenografts.

Diet as a Potential Moderator for Genome Stability and Immune Response in Pediatric Leukemia.

Pediatric leukemias are the most prevalent cancers affecting children in developed societies, with childhood acute lymphoblastic leukemia (ALL) being the most common subtype. As diet is a likely modulator of many diseases, this review focuses on the potential for diet to influence the incidence and progression of childhood ALL. In particular, the potential effect of diets on genome stability and immunity during the prenatal and postnatal stages of early childhood development are discussed.

The Relationship Between the Development of General Offending and Intimate Partner Violence Perpetration in Young Adulthood.

This study examined how patterns in general offending relate to the occurrence of and likelihood of persistence in intimate partner violence (IPV) perpetration in young adulthood. The study used longitudinal data from the cohort of 18 year olds from the Project on Human Development in Chicago Neighborhoods study. Self-reported offending was measured in all three waves, and data on IPV were collected in Waves 1 and 3.

Development of a Polarizable Interatomic Potential for Molten Lithium, Sodium, and Potassium Nitrate.

A polarizable interatomic potential is developed for atomistic simulations of molten MNO (M = Li, Na, K) salts. The potential is parametrized using a force matching method relying on the adjustment of parameters such that density functional theory generated forces, stress tensors, and dipole moments are reproduced. Simulations conducted using the new potential are used to estimate physical parameters of the melt, which are then compared with available experimental results.

Hyaluronan Mediated Motility Receptor (HMMR) Encodes an Evolutionarily Conserved Homeostasis, Mitosis, and Meiosis Regulator Rather than a Hyaluronan Receptor.

Hyaluronan is an extracellular matrix component that absorbs water in tissues and engages cell surface receptors, like Cluster of Differentiation 44 (CD44), to promote cellular growth and movement. Consequently, CD44 demarks stem cells in normal tissues and tumor-initiating cells isolated from neoplastic tissues. Hyaluronan mediated motility receptor (HMMR, also known as RHAMM) is another one of few defined hyaluronan receptors.

A Model of Differential Mammary Growth Initiation by Stat3 and Asymmetric Integrin-α6 Inheritance.

Multiple cancer-related genes both promote and paradoxically suppress growth initiation, depending on the cell context. We discover an explanation for how this occurs for one such protein, Stat3, based on asymmetric cell division. Here, we show that Stat3, by Stathmin/PLK-1, regulates mitotic spindle orientation, and we use it to create and test a model for differential growth initiation.

Daily Context for Abusive and Neglectful Behavior in Family Caregiving for Dementia.

Background And Objectives: The purpose of this study was to identify risk and protective factors for abusive and neglectful behavior in the context of daily caregiving.

Research Design And Methods: Family caregivers who co-reside with a care recipient with Alzheimer's disease and related dementia, recruited from social media, completed 21-days of diaries. Multilevel modeling with days (n = 831) nested within caregivers (N = 50) was used to evaluate relationships between hypothesized risk and protective factors and the odds of an abusive or neglectful behavior on a given day.

FAM83D directs protein kinase CK1α to the mitotic spindle for proper spindle positioning.

The concerted action of many protein kinases helps orchestrate the error-free progression through mitosis of mammalian cells. The roles and regulation of some prominent mitotic kinases, such as cyclin-dependent kinases, are well established. However, these and other known mitotic kinases alone cannot account for the extent of protein phosphorylation that has been reported during mammalian mitosis.

Management of exposed pacemaker caused by burns.

Annual implants of cardiovascular implantable devices (CIEDs) are increasing, thus increasing the risk of device exposure. This case presents CIED management issues following traumatic thermal injury. A 59-year-old female presented to intensive care with 42% total body surface area burn involving tissue over her pacemaker generator.